Population- and Variant-Based Genome Analyses of Viruses from Vaccine-Derived Rabies Cases Demonstrate Product Specific Clusters and Unique Patterns
Sten Calvelage,
Marcin Smreczak,
Anna Orłowska,
Conrad Martin Freuling,
Thomas Müller,
Christine Fehlner-Gardiner,
Susan Nadin-Davis,
Dirk Höper,
Paweł Trębas
Affiliations
Sten Calvelage
Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany
Marcin Smreczak
Department of Virology, National Veterinary Research Institute, 24-100 Puławy, Poland
Anna Orłowska
Department of Virology, National Veterinary Research Institute, 24-100 Puławy, Poland
Conrad Martin Freuling
Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, WHO Collaborating Centre for Rabies Surveillance and Research, OIE Reference Laboratory for Rabies, 17493 Greifswald-Insel Riems, Germany
Thomas Müller
Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, WHO Collaborating Centre for Rabies Surveillance and Research, OIE Reference Laboratory for Rabies, 17493 Greifswald-Insel Riems, Germany
Christine Fehlner-Gardiner
National Reference Centre for Rabies, Ottawa Laboratory–Fallowfield, Canadian Food Inspection Agency, Ottawa, ON K2H 8P91, Canada
Susan Nadin-Davis
National Reference Centre for Rabies, Ottawa Laboratory–Fallowfield, Canadian Food Inspection Agency, Ottawa, ON K2H 8P91, Canada
Dirk Höper
Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany
Paweł Trębas
Department of Virology, National Veterinary Research Institute, 24-100 Puławy, Poland
Rabies in wildlife has been successfully controlled in parts of Europe and North America using oral rabies vaccination, i.e., the distribution of baits containing live-attenuated virus strains. Occasionally, these vaccines caused vaccine virus-induced rabies cases. To elucidate the mechanisms of genetic selection and the effect of viral populations on these rabies cases, a next generation sequencing approach as well as comprehensive data analyses of the genetic diversity of Street Alabama Dufferin (SAD) and ERA vaccine virus strains and vaccine-induced rabies cases from Canada and several European countries were conducted. As a result, twelve newly generated sets of sequencing data from Canada and Poland were added to a pool of previously investigated samples. While the population-based analysis showed a segregation of viruses of ERA vaccine-induced rabies cases from those of SAD Bern original (SAD Bernorig)-derived rabies cases, the in-depth variant analysis revealed three distinct combinations of selected variants for the ERA vaccine-induced cases, suggesting the presence of multiple replication-competent haplotypes in the investigated ERA-BHK21 vaccine. Our findings demonstrate the potential of a deep sequencing approach in combination with comprehensive analyses on the consensus, population, and variant level.
